I read with great interest the report from Cross and colleagues1 entitled “Bevacizumabmediated interference with VEGF signaling is sufficient to induce a preeclampsia-like syndrome in non-pregnant women.”1 In both reported cases, bevacizumab-induced alteration of vascular endothelial growth factor (VEGF) is purported to contribute to a constellation of clinical and radiologic features closely resembling that of preeclampsia. The authors describe this phenomenon as a preeclampsia-like syndrome characterized by reversible posterior leukoencephalopathy on imaging, along with associated neurologic manifestations (headache, vision changes, and seizure), hypertension, and laboratory abnormalities including hepatic dysfunction. I posit that these changes may be encompassed by a diagnosis of posterior reversible encephalopathy syndrome (PRES), alternatively referred to as reversible posterior leukoencephalopathy syndrome in much of the obstetric literature.
The characteristic imaging findings of PRES are virtually ubiquitous in the eclampsia population and thus represent a key feature of the eclampsia disease spectrum.2 Although pregnancy is recognized as a significant contributing factor for the development of PRES, various other predisposing conditions, including sepsis, transplantation, autoimmune disease, and cancer chemotherapy, are encountered. 3 The clinicoradiologic manifestations of PRES are thought to stem from an underlying state of immune activation/dysfunction characterized by proinflammatory cytokines and vasoactive factors that lead to endothelial dysfunction, vasoconstriction, and tissue hypoperfusion.4,5 Given that alterations in VEGF are thought to play a role in the development of characteristic brain edema in these patients,6,7 it is not surprising that bevacizumab has been increasingly cited as a contributing factor in PRES.8–10
Recognition of the role VEGF signaling plays in the pathophysiology of eclampsia/preeclampsia has advanced general understanding of this common phenomenon.11 Although the clinicoradiologic features manifested by VEGF-treated patients reported by Cross and colleagues1 certainly mimic those of preeclampsia, we feel that it is unnecessary to invoke a novel preeclampsia-like syndrome when this spectrum of findings can be adequately explained by the systemic toxicity state known as PRES. As our understanding of PRES grows, it seems increasingly apparent that all of the known PRES-predisposing factors (including pregnancy) may elicit an immune-mediated cascade that leads to a common pathophysiology and disease phenotype. Going forward, an approach that views PRES patients encountered by clinicians from various disciplines (eg, obstetrics, neurology, oncology) in a more cohesive manner may be a more productive manner in which to study and eventually better understand the pathophysiology of PRES.
References
- 1.Cross SN, Ratner E, Rutherford TJ, et al. Bevacizumabmediated interference with VEGF signaling is sufficient to induce a preeclampsia-like syndrome in nonpregnant women. Rev Obstet Gynecol. 2012;5:2–8. [PMC free article] [PubMed] [Google Scholar]
- 2.Brewer J, Owens MY, Wallace K, et al. Posterior reversible encephalopathy syndrome in 46 of 47 patients with eclampsia. Am J Obstet Gynecol. 2013;208:468.e1–468.e6. doi: 10.1016/j.ajog.2013.02.015. [DOI] [PubMed] [Google Scholar]
- 3.Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol. 2008;29:1036–1042. doi: 10.3174/ajnr.A0928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol. 2008;29:1043–1049. doi: 10.3174/ajnr.A0929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Bartynski WS, Boardman JF. Catheter angiography, MR angiography, and MR perfusion in posterior reversible encephalopathy syndrome. AJNR Am J Neuroradiol. 2008;29:447–455. doi: 10.3174/ajnr.A0839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kofler J, Bartynski WS, Reynolds TQ, et al. Posterior reversible encephalopathy syndrome (PRES) with immune system activation, VEGF up-regulation, and cerebral amyloid angiopathy. J Comput Assist Tomogr. 2011;35:39–42. doi: 10.1097/RCT.0b013e3181f31917. [DOI] [PubMed] [Google Scholar]
- 7.Horbinski C, Bartynski WS, Carson-Walter E, et al. Reversible encephalopathy after cardiac transplantation: histologic evidence of endothelial activation, T-cell specific trafficking, and vascular endothelial growth factor expression. AJNR Am J Neuroradiol. 2009;30:588–590. doi: 10.3174/ajnr.A1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Seet RC, Rabinstein AA. Clinical features and outcomes of posterior reversible encephalopathy syndrome following bevacizumab treatment. QJM. 2012;105:69–75. doi: 10.1093/qjmed/hcr139. [DOI] [PubMed] [Google Scholar]
- 9.Dersch R, Stich O, Goller K, et al. Atypical posterior reversible encephalopathy syndrome associated with chemotherapy with bevacizumab, gemcitabine, and cisplatin. J Neurol. 2013;260:1406–1407. doi: 10.1007/s00415-013-6866-6. [DOI] [PubMed] [Google Scholar]
- 10.Chang Y, Mbeo G, Littman SJ. Reversible posterior leukoencephalopathy syndrome associated with concurrent bevacizumab, gemcitabine, and oxaliplatin for cholangiocarcinoma. J Gastrointest Cancer. 2012;43:505–507. doi: 10.1007/s12029-011-9279-8. [DOI] [PubMed] [Google Scholar]
- 11.Myatt L, Webster RP. Vascular biology of preeclampsia. J Thromb. Haemost. 2009;7:375–384. doi: 10.1111/j.1538-7836.2008.03259.x. [DOI] [PubMed] [Google Scholar]